ArticleJournal of molecular medicine (Berlin, Germany)2013
Dichloroacetate reverses the hypoxic adaptation to bevacizumab and enhances its antitumor effects in mouse xenografts.
Article in Journal of molecular medicine (Berlin, Germany), 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
48 citing papers in PubMed, 73 citations in OpenAlex.
- Metal thiosemicarbazonates as dual mR2 RNR and colchicine-site tubulin inhibitors: from biochemical inhibition to mitotic arrest in MCF-7 breast cancer cells.Inorganic chemistry frontiers · 2026Article
- Simvastatin reprograms lipid metabolism in B16.F10 melanoma cells to favor an early resistant phenotype.Scientific reports · 2026Article
- In Vivo and In Vitro Experimental Study Comparing the Effect of a Combination of Sodium Dichloroacetate and Valproic Acid with That of Temozolomide on Adult Glioblastoma.International journal of molecular sciences · 2025Article
- Targeting Tumor Hypoxia with Nanoparticle-Based Therapies: Challenges, Opportunities, and Clinical Implications.Pharmaceuticals (Basel, Switzerland) · 2024Review
- Matrix Protein of Vesicular Stomatitis Virus Targets the Mitochondria, Reprograms Glucose Metabolism, and Sensitizes to 2-Deoxyglucose in Glioblastoma.Human gene therapy · 2024Article
- In Vitro Cytotoxic Potential and In Vivo Antitumor Effects of NOS/PDK-Inhibitor T1084.International journal of molecular sciences · 2024Article
- Dichloroacetate for Cancer Treatment: Some Facts and Many Doubts.Pharmaceuticals (Basel, Switzerland) · 2024Review
- PP2A-based triple-strike therapy overcomes mitochondrial apoptosis resistance in brain cancer cells.Molecular oncology · 2023Article
- Article
- Mitochondrial dysfunctions in T cells: focus on inflammatory bowel disease.Frontiers in immunology · 2023Review
- Hypoxia signaling: Challenges and opportunities for cancer therapy.Seminars in cancer biology · 2022Review
- Article
- Combination of NOS- and PDK-Inhibitory Activity: Possible Way to Enhance Antitumor Effects.International journal of molecular sciences · 2022Article
- Targeting Glucose Metabolism of Cancer Cells with Dichloroacetate to Radiosensitize High-Grade Gliomas.International journal of molecular sciences · 2021Review
- Critical role of Aquaporin-1 and telocytes in infantile hemangioma response to propranolol beta blockade.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Classic and targeted anti-leukaemic agents interfere with the cholesterol biogenesis metagene in acute myeloid leukaemia: Therapeutic implications.Journal of cellular and molecular medicine · 2020Article
- Adapt and conquer: Metabolic flexibility in cancer growth, invasion and evasion.Molecular metabolism · 2020Review
- Metabolic Plasticity of Tumor Cells: How They Do Adapt to Food Deprivation.Advances in experimental medicine and biology · 2020Review
- Resistance to Anti-angiogenic Therapies: A Mechanism Depending on the Time of Exposure to the Drugs.Frontiers in cell and developmental biology · 2020Review
- Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
14 authors at 5 institutions in 3 countries.
Funding
Abstract
Inhibition of vascular endothelial growth factor increases response rates to chemotherapy and progression-free survival in glioblastoma. However, resistance invariably occurs, prompting the urgent need for identification of synergizing agents. One possible strategy is to understand tumor adaptation to microenvironmental changes induced by antiangiogenic drugs and test agents that exploit this process. We used an in vivo glioblastoma-derived xenograft model of tumor escape in presence of continuous treatment with bevacizumab. U87-MG or U118-MG cells were subcutaneously implanted into either BALB/c SCID or athymic nude mice. Bevacizumab was given by intraperitoneal injection every 3 days (2.5 mg/kg/dose) and/or dichloroacetate (DCA) was administered by oral gavage twice daily (50 mg/kg/dose) when tumor volumes reached 0.3 cm(3) and continued until tumors reached approximately 1.5-2.0 cm(3). Microarray analysis of resistant U87 tumors revealed coordinated changes at the level of metabolic genes, in particular, a widening gap between glycolysis and mitochondrial respiration. There was a highly significant difference between U87-MG-implanted athymic nude mice 1 week after drug treatment. By 2 weeks of treatment, bevacizumab and DCA together dramatically blocked tumor growth compared to either drug alone. Similar results were seen in athymic nude mice implanted with U118-MG cells. We demonstrate for the first time that reversal of the bevacizumab-induced shift in metabolism using DCA is detrimental to neoplastic growth in vivo. As DCA is viewed as a promising agent targeting tumor metabolism, our data establish the timely proof of concept that combining it with antiangiogenic therapy represents a potent antineoplastic strategy.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.